The aim of the proposed study is to gain a more complete understanding of chemical carcinogenesis by selected polycyclic aromatic hydrocarbons and the genetic basis for differences in susceptibility between relatively resistant and highly susceptible strains of inbred rats. The compounds to be studied are 7-hydroxymethyl-, 7-iodomethyl-, 7-bromomethyl-, 7-chloromethyl-, 7-benzoyloxymethyl-, 7-acetoxymethyl-, 7-formly-, and 7-methoxymethyl-12methylbenz(a)- anthracene and 4-methoxy-7, 12-dimethylbenz(a) anthracene. The relative carcinogenicity of this closely related series of compounds will be determined by repeated subcutaneous injection in rat strains of high and low susceptibility at equimolar doses. The metabolism of each of the compounds will be studied in vitro and in vivo to determine the conversion to 7-hydroxylmethyl-12-methylbenz(a) anthracene by tissue homogenates (liver, site of injection) of rat strains of high and low susceptibility. Binding of radioactive hydrocarbons to DNA, RNA and proteins of tissues from rat strains of high and low susceptibility will be studied to determine whether there is a relationship between binding and carcinogenic potency. The use of inbred strains from the same laboratory will permit a clearer definition of which factors are relevant to the induction of cancer by polycyclic hydrocarbons, and how genetic control determines the chemical induction of cancer.